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Annual Review of Pathology-Mechanisms of Disease最新文献

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Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders.
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathol-051220-092001
Mehmet M Altintas, Shivangi Agarwal, Yashwanth Sudhini, Ke Zhu, Changli Wei, Jochen Reiser
{"title":"Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders.","authors":"Mehmet M Altintas, Shivangi Agarwal, Yashwanth Sudhini, Ke Zhu, Changli Wei, Jochen Reiser","doi":"10.1146/annurev-pathol-051220-092001","DOIUrl":"10.1146/annurev-pathol-051220-092001","url":null,"abstract":"<p><p>Focal segmental glomerulosclerosis (FSGS) is the morphologic manifestation of a spectrum of kidney diseases that primarily impact podocytes, cells that create the filtration barrier of the glomerulus. As its name implies, only parts of the kidney and glomeruli are affected, and only a portion of the affected glomerulus may be sclerosed. Although the diagnosis is based primarily on microscopic features, patient stratification relies on clinical data such as proteinuria and etiological criteria. FSGS affects both children and adults and has an elevated risk of progression to end-stage renal disease. The prevalence of FSGS is rising among various populations, and the efficacy of various therapies is limited. Therefore, understanding the pathophysiology of FSGS and developing targeted therapies to address the complex needs of FSGS patients are topics of great interest that are currently being studied across various clinical trials. We discuss the etiology of FSGS, describe the major contributing pathophysiological pathways, and outline emerging therapeutic strategies along with their pitfalls.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"329-353"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Apoptosis in Cancer Biology and Therapy.
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 DOI: 10.1146/annurev-pathmechdis-051222-115023
Allison Moyer, Kosuke Tanaka, Emily H Cheng
{"title":"Apoptosis in Cancer Biology and Therapy.","authors":"Allison Moyer, Kosuke Tanaka, Emily H Cheng","doi":"10.1146/annurev-pathmechdis-051222-115023","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-051222-115023","url":null,"abstract":"<p><p>Since its inception, the study of apoptosis has been intricately linked to the field of cancer. The term apoptosis was coined more than five decades ago following its identification in both healthy tissues and malignant neoplasms. The subsequent elucidation of its molecular mechanisms has significantly enhanced our understanding of how cancer cells hijack physiological processes to evade cell death. Moreover, it has shed light on the pathways through which most anticancer therapeutics induce tumor cell death, including targeted therapy and immunotherapy. These mechanistic studies have paved the way for the development of therapeutics directly targeting either pro- or antiapoptotic proteins. Notably, the US Food and Drug Administration (FDA) approved the BCL-2 inhibitor venetoclax in 2016, with additional agents currently undergoing clinical trials. Recent research has brought to the forefront both the anti- and proinflammatory effects of individual apoptotic pathways. This underscores the ongoing imperative to deepen our comprehension of apoptosis, particularly as we navigate the evolving landscape of immunotherapy.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"20 1","pages":"303-328"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Challenges and Opportunities in the Clinical Translation of High-Resolution Spatial Transcriptomics. 高分辨率空间转录组学临床转化的挑战与机遇。
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023417
Tancredi Massimo Pentimalli, Nikos Karaiskos, Nikolaus Rajewsky
{"title":"Challenges and Opportunities in the Clinical Translation of High-Resolution Spatial Transcriptomics.","authors":"Tancredi Massimo Pentimalli, Nikos Karaiskos, Nikolaus Rajewsky","doi":"10.1146/annurev-pathmechdis-111523-023417","DOIUrl":"10.1146/annurev-pathmechdis-111523-023417","url":null,"abstract":"<p><p>Pathology has always been fueled by technological advances. Histology powered the study of tissue architecture at single-cell resolution and remains a cornerstone of clinical pathology today. In the last decade, next-generation sequencing has become informative for the targeted treatment of many diseases, demonstrating the importance of genome-scale molecular information for personalized medicine. Today, revolutionary developments in spatial transcriptomics technologies digitalize gene expression at subcellular resolution in intact tissue sections, enabling the computational analysis of cell types, cellular phenotypes, and cell-cell communication in routinely collected and archival clinical samples. Here we review how such molecular microscopes work, highlight their potential to identify disease mechanisms and guide personalized therapies, and provide guidance for clinical study design. Finally, we discuss remaining challenges to the swift translation of high-resolution spatial transcriptomics technologies and how integration of multimodal readouts and deep learning approaches is bringing us closer to a holistic understanding of tissue biology and pathology.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"405-432"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNA Damage Responses in Cellular Homeostasis, Genome Stability, and Disease. 细胞稳态、基因组稳定性和疾病中的 RNA 损伤反应
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1146/annurev-pathmechdis-111523-023516
Hani S Zaher, Nima Mosammaparast
{"title":"RNA Damage Responses in Cellular Homeostasis, Genome Stability, and Disease.","authors":"Hani S Zaher, Nima Mosammaparast","doi":"10.1146/annurev-pathmechdis-111523-023516","DOIUrl":"10.1146/annurev-pathmechdis-111523-023516","url":null,"abstract":"<p><p>All cells are exposed to chemicals that can damage their nucleic acids. Cells must protect these polymers because they code for key factors or complexes essential for life. Much of the work on nucleic acid damage has naturally focused on DNA, partly due to the connection between mutagenesis and human disease, especially cancer. Recent work has shed light on the importance of RNA damage, which triggers a host of conserved RNA quality control mechanisms. Because many RNA species are transient, and because of their ability to be retranscribed, RNA damage has largely been ignored. Yet, because of the connection between damaged RNA and DNA during transcription, and the association between essential complexes that process or decode RNAs, notably spliceosomes and ribosomes, the appropriate handling of damaged RNAs is critical for maintaining cellular homeostasis. This notion is bolstered by disease states, including neurodevelopmental and neurodegenerative diseases, that may arise upon loss or misregulation of RNA quality control mechanisms.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":" ","pages":"433-457"},"PeriodicalIF":28.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circadian Clocks, Daily Stress, and Neurodegenerative Disease 昼夜节律、日常压力与神经退行性疾病
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-10-18 DOI: 10.1146/annurev-pathmechdis-031521-033828
Eugene Nyamugenda, Clark Rosensweig, Ravi Allada
{"title":"Circadian Clocks, Daily Stress, and Neurodegenerative Disease","authors":"Eugene Nyamugenda, Clark Rosensweig, Ravi Allada","doi":"10.1146/annurev-pathmechdis-031521-033828","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-031521-033828","url":null,"abstract":"Disrupted circadian or 24-h rhythms are among the most common early findings in a wide range of neurodegenerative disorders. Once thought to be a mere consequence of the disease process, increasing evidence points toward a causal or contributory role of the circadian clock in neurodegenerative disease. Circadian clocks control many aspects of cellular biochemistry, including stress pathways implicated in neuronal survival and death. Given the dearth of disease-modifying therapies for these increasingly prevalent disorders, this understanding may lead to breakthroughs in the development of new treatments. In this review, we provide a background on circadian clocks and focus on some potential mechanisms that may be pivotal in neurodegeneration.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"109 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiple System Atrophy: Pathology, Pathogenesis, and Path Forward 多系统萎缩：病理学、发病机制和前进之路
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-10-15 DOI: 10.1146/annurev-pathmechdis-051122-104528
Alain Ndayisaba, Glenda M. Halliday, Vikram Khurana
{"title":"Multiple System Atrophy: Pathology, Pathogenesis, and Path Forward","authors":"Alain Ndayisaba, Glenda M. Halliday, Vikram Khurana","doi":"10.1146/annurev-pathmechdis-051122-104528","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-051122-104528","url":null,"abstract":"Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by autonomic failure and motor impairment. The hallmark pathologic finding in MSA is widespread oligodendroglial cytoplasmic inclusions rich in aggregated α-synuclein (αSyn). MSA is widely held to be an oligodendroglial synucleinopathy, and we outline lines of evidence to support this assertion, including the presence of early myelin loss. We consider emerging data that support the possibility of neuronal or immune dysfunction as primary drivers of MSA. These hypotheses are placed in the context of a major recent discovery that αSyn is conformationally distinct in MSA versus other synucleinopathies such as Parkinson's disease. We outline emerging techniques in epidemiology, genetics, and molecular pathology that will shed more light on this mysterious disease. We anticipate a future in which cutting-edge developments in personalized disease modeling, including with pluripotent stem cells, bridge mechanistic developments at the bench and real benefits at the bedside.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"103 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogenesis of Germinal Matrix Hemorrhage: Insights from Single-Cell Transcriptomics. 胚芽基质出血的发病机制：单细胞转录组学的启示。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-10-14 DOI: 10.1146/annurev-pathmechdis-111523-023446
Jiapei Chen,Jennifer Ja-Yoon Choi,Pin-Yeh Lin,Eric J Huang
{"title":"Pathogenesis of Germinal Matrix Hemorrhage: Insights from Single-Cell Transcriptomics.","authors":"Jiapei Chen,Jennifer Ja-Yoon Choi,Pin-Yeh Lin,Eric J Huang","doi":"10.1146/annurev-pathmechdis-111523-023446","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023446","url":null,"abstract":"The germinal matrix harbors neurogenic niches in the subpallium of the prenatal human brain that produce abundant GABAergic neurons. In preterm infants, the germinal matrix is particularly vulnerable to developing hemorrhage, which disrupts neurogenesis and causes severe neurodevelopmental sequelae. However, the disease mechanisms that promote germinal matrix hemorrhage remain unclear. Here, we review recent advances using single-cell transcriptomics to uncover novel mechanisms that govern neurogenesis and angiogenesis in the germinal matrix of the prenatal human brain. These approaches also reveal the critical role of immune-vascular interaction that promotes vascular morphogenesis in the germinal matrix and how proinflammatory factors from activated neutrophils and monocytes can disrupt this process, leading to hemorrhage. Collectively, these results reveal fundamental disease mechanisms and therapeutic interventions for germinal matrix hemorrhage.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"1 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cysteinyl Leukotrienes in Allergic Inflammation 过敏性炎症中的胱氨酰白三烯
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-10-07 DOI: 10.1146/annurev-pathmechdis-111523-023509
Minkyu Lee, Joshua A. Boyce, Nora A. Barrett
{"title":"Cysteinyl Leukotrienes in Allergic Inflammation","authors":"Minkyu Lee, Joshua A. Boyce, Nora A. Barrett","doi":"10.1146/annurev-pathmechdis-111523-023509","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023509","url":null,"abstract":"The cysteinyl leukotrienes (CysLTs), LTC4, LTD4, and LTE4, are potent lipid mediators derived from arachidonic acid through the 5-lipoxygenase pathway. These mediators produce both inflammation and bronchoconstriction through three distinct G protein–coupled receptors (GPCRs)—CysLT1, CysLT2, and OXGR1 (also known as CysLT3 or GPR99). While CysLT-mediated functions in the effector phase of allergic inflammation and asthma have been established for some time, recent work has demonstrated novel roles for these mediators and their receptors in the induction and amplification of type 2 inflammation. Additionally, in vitro studies and murine models have uncovered diverse regulatory mechanisms that restrain or amplify CysLT receptor activation and CysLT receptor function. This review provides an overview of CysLT biosynthesis and its regulation, the molecular and functional pharmacology of CysLT receptors, and an overview of the established and emerging roles of CysLTs in asthma, aspirin-exacerbated respiratory disease, and type 2 inflammation.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"249 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
B Cell Responses to the Placenta and Fetus B 细胞对胎盘和胎儿的反应
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-09-12 DOI: 10.1146/annurev-pathmechdis-111523-023459
Gabrielle Rizzuto
{"title":"B Cell Responses to the Placenta and Fetus","authors":"Gabrielle Rizzuto","doi":"10.1146/annurev-pathmechdis-111523-023459","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023459","url":null,"abstract":"Pregnancy has fascinated immunologists ever since Peter Medawar's observation that reproduction runs contrary to the founding tenets of immunology. During healthy pregnancy, maternal B cells interact with antigens of the foreign conceptus (placenta and fetus) yet do not elicit rejection. Instead, robust, and redundant fetomaternal tolerance pathways generally prevent maternal B cells and antibodies from harming the placenta and fetus. Fetomaternal tolerance is not absolute, and unfortunately there exist several pregnancy complications that arise from breaks therein. Here, important historic and recent developments in the field of fetomaternal tolerance pertaining to maternal B cells and antibodies are reviewed. General rules from which to conceptualize humoral tolerance to the placenta and fetus are proposed. Significant but underexplored ideas are highlighted and topics for future research are suggested, findings from which are predicted to provide insight into the fundamental nature of tolerance and bolster efforts to combat immune-mediated pregnancy complications.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"9 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wnt/β-Catenin Signaling in Liver Pathobiology 肝脏病理生物学中的 Wnt/β-Catenin 信号转导
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-09-11 DOI: 10.1146/annurev-pathmechdis-111523-023535
Matthew D. Carson, Kari Nejak-Bowen
{"title":"Wnt/β-Catenin Signaling in Liver Pathobiology","authors":"Matthew D. Carson, Kari Nejak-Bowen","doi":"10.1146/annurev-pathmechdis-111523-023535","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023535","url":null,"abstract":"The liver has a critical role in regulating host metabolism, immunity, detoxification, and homeostasis. Proper liver function is essential for host health, and dysregulation of hepatic signaling pathways can lead to the onset of disease. The Wnt/β-catenin signaling pathway is an important regulator of liver homeostasis and function. Throughout life, hepatic Wnt/β-catenin signaling contributes to liver development and growth, metabolic zonation, and regeneration. Extensive research has demonstrated that aberrant Wnt/β-catenin signaling drives liver pathologies, including cancers, steatohepatitis, and cholestasis. In this review, we discuss the Wnt/β-catenin pathway as it pertains to liver function and how disruptions in this pathway contribute to the onset and progression of liver diseases. Further, we discuss ongoing research that targets the Wnt/β-catenin pathway for the treatment of liver pathologies.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"7 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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